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Urinary epidermal growth factor as a prognostic marker for the progression of Alport syndrome in children.

AbstractBACKGROUND:
Alport syndrome is a rare hereditary kidney disease manifested with progressive renal failure. Considerable variation exists in terms of disease progression among patients with Alport syndrome. Identification of patients at high risk of rapid progression remains an unmet need. Urinary epidermal growth factor (uEGF) has been shown to be independently associated with risk of progression to adverse kidney outcome in multiple independent adult chronic kidney disease (CKD) cohorts. In this study, we aim to assess if uEGF is associated with kidney impairment and its prognostic value for children with Alport syndrome.
METHODS:
One hundred and seventeen pediatric patients with Alport syndrome and 146 healthy children (3-18 years old) were included in this study. uEGF was measured in duplicates in baseline urine samples using ELISA (R&D) and concentration was normalized by urine creatinine (uEGF/Cr). In patients with longitudinal follow-up data (n = 38), progression was defined as deteriorated kidney function (CKD stage increase) during follow-up period (follow-up length is about 31 months in average). The association of baseline uEGF/Cr level with estimated glomerular filtration rate (eGFR) slope and Alport syndrome patients' progression to a more advanced CKD stage during the follow-up period was used to evaluate the prognostic value of the marker.
RESULTS:
We found that uEGF/creatinine (uEGF/Cr) decreases with age in pediatric patients with Alport syndrome with a significantly faster rate than in healthy children of the same age group. uEGF/Cr is significantly correlated with eGFR (r = 0.75, p < 0.001), after adjustment for age. In 38 patients with longitudinal follow-up, we observed a significant correlation between uEGF/Cr and eGFR slope (r = 0.58, p < 0.001). Patients with lower uEGF/Cr level were at increased risk of progression to a higher CKD stage. uEGF/Cr was able to distinguish progressors from non-progressors with an AUC of 0.88, versus 0.77 by eGFR and 0.81 by 24-h urinary protein (24-h UP).
CONCLUSIONS:
Our study suggests that uEGF/Cr is a promising biomarker for accelerated kidney function decline in pediatric patients with Alport syndrome. It may help to identify patients at high risk of progression for targeted clinical care and improve the patients' stratification in interventional trials.
AuthorsBaihong Li, Yanqin Zhang, Fang Wang, Viji Nair, Fangrui Ding, Huijie Xiao, Yong Yao, Matthias Kretzler, Wenjun Ju, Jie Ding
JournalPediatric nephrology (Berlin, Germany) (Pediatr Nephrol) Vol. 33 Issue 10 Pg. 1731-1739 (10 2018) ISSN: 1432-198X [Electronic] Germany
PMID29948307 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Biomarkers
  • Epidermal Growth Factor
  • Creatinine
Topics
  • Adolescent
  • Age Factors
  • Biomarkers (urine)
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Creatinine (urine)
  • Disease Progression
  • Epidermal Growth Factor (urine)
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate
  • Humans
  • Kidney Failure, Chronic (diagnosis, pathology, urine)
  • Kidney Function Tests (methods)
  • Male
  • Nephritis, Hereditary (diagnosis, pathology, urine)
  • Prognosis
  • Risk Assessment (methods)
  • Severity of Illness Index

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